Evaluation of Type 2 Diabetes Risk Variants (Alleles) in the Pashtun Ethnic Population of Pakistan





type 2 diabetes, risk variants, bioinformatics, whole exome sequencing, Pashtun population


Objective.  To evaluate  the Type 2 Diabetes (T2D) risk variants in the Phastun ethnic population of Khyber Pakhtunkhwa using the nascent whole-exome sequencing (WES) to better understand the pathogenesis of this complex polygenic disorder.

Methodology. A total of 100 confirmed patients with T2D of Pashtun ethnicity were included in the study, DNA was extracted from whole blood samples, and paired-end libraries were prepared using the Illumina Nextera XT DNA library kit carefully following the manufacturer’s instructions. Illumina HiSeq 2000 was used to obtain sequences of the prepared libraries followed by bioinformatics data analysis.

Results. A total of  n=11 pathogenic/likely pathogenic varinats were reported  in the CAP10, PAX4, IRS-2, NEUROD1, CDKL1 and WFS1. Among the reported variants CAP10/rs55878652 (c.1990-7T>C; p.Leu446Pro) and CAP10/ rs2975766 (c.1996A>G; p.Ile666Val)  identified were novel, and have not yet been reported for any disease in the database.

The variants CAP10/rs7607759 (c.1510A>G, p.Thr504Ala), PAX4/rs712701 (c.962A>C; p.His321Pro), PAX4/rs772936097 (c.748-3delT; p.Arg325Trp), IRS-2/rs1805097 (c.3170G>A; p.Gly1057Asp), NEUROD1/rs1801262 (c.133A>G; p.Thr45Ala), CDKL1/rs77152992 (c.1226C>T; p.Pro409Leu), WFS1/rs1801212 (c.997G>A; p.Val333Ile), WFS1/rs1801208 (c.1367G>A; p.Arg456His), and WFS1/rs734312 (c.1832G>A; p.Arg611His)  are previously identified in other ethnic populations. Our study reconfirms the  associations of these variants with T2D  in Pakistani Pashtun population.

Conclusion. In-silico analysis of  exome sequencing  data suggest a statistically substantial association  of all (n=11)  identified variants with T2D in the Pashtun ethnic population. This study may serve as a foundation for performing future molecular studies aimed at unraveling T2D associated genes.


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Author Biographies

Asif Jan, University of Peshawar, Pakistan

Department of Pharmacy

Muhammad Saeed, University of Peshawar, Pakistan

Professor, Department of Pharmacy

Zakiullah, University of Peshawar, Pakistan

Department of Pharmacy

Rani Akbar, Adul Wali Khan University Mardan, Pakistan

Department of Pharmacy

Hamayun Khan, Islam College of Pharmacy, Gujranwala, Punjab, Pakistan



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How to Cite

Jan, A., Saeed, M., Zakiullah, Akbar, R., & Khan, H. (2021). Evaluation of Type 2 Diabetes Risk Variants (Alleles) in the Pashtun Ethnic Population of Pakistan. Journal of the ASEAN Federation of Endocrine Societies, 38(S1). https://doi.org/10.15605/jafes.037.S3